Small increase in medication may play a big part in helping smokers quit

BY
Clayton Boldt, Ph.D.

Increasing the dosage of a prescription smoking cessation medication by 1 milligram a day – from 2 to 3 milligrams – more than doubled abstinence rates after three months in some patients, according to research from MD Anderson Cancer Center.

The findings, published in the Journal of Clinical Psychopharmacology, found that this relatively small increase in varenicline benefited patients taking who had managed to cut down on smoking, but not quit completely. The dose increase also offered prolonged benefits at six- and nine-month follow-ups, with minimal side effects.

Tobacco use remains the leading preventable cause of death and the leading cause of cancer in the U.S. Further, many studies have shown improved outcomes after quitting smoking for those already diagnosed with cancer.

MD Anderson’s Tobacco Treatment Program (TTP) provides evidence-based tobacco cessation services, including counseling and medications, at no cost to MD Anderson patients, employees and their families. The program’s team also conducts clinical trials testing innovative approaches, such as this study, to improving cessation rates. These trials are open to the public.

In multiple studies, varenicline offers improved cessation rates relative to other medications, but more than half of smokers still fail to quit at the end of their treatment, explained lead author Maher Karam-Hage, M.D., professor of Behavioral Science and associate medical director of the TTP.

“It is important to understand how we might continue to help our patients who are not able to completely quit smoking before they become discouraged and stop trying,” said Karam-Hage. “In many cases, patients treated with varenicline are able to reduce their daily cigarette usage significantly despite not achieving abstinence, but it has not been clear if an increased dose would be beneficial to them to get to quit.”

Based on those results, the researchers wanted to see if increasing varenicline dosage would improve cessation rates among those who had initially shown a favorable response to the medication. Favorable initial response was defined as having reduced daily cigarette consumption by at least half.

For the non-randomized, open-label study, TTP patients previously treated with varenicline and having had a favorable response after six weeks were offered the option of increasing their dose. A total of 429 patients participated in the study, with 356 receiving 2 mg/day and 73 receiving 3 mg/day for at least an additional four weeks. All patients received similar counseling during the trial, and researchers followed up with them after three, six and nine months.

Three months after increasing their dosage, 26% of patients receiving 3 mg/day reported not smoking in the previous seven days, compared to 11.5% of those taking 2 mg/day. This difference was statistically significant, and the differences in abstinence rates remained significant six and nine months later.

Importantly, there were no significant differences in the likelihood of side effects between groups. At least one adverse event was reported by 31.5% of those taking an increased dosage, compared to 34.5% of those taking the standard dosage. In addition, none of the side effects reported were severe or serious. Only mild or moderate side effects such as nausea, abnormal dreams, insomnia and headaches were reported.

“Our data support the hypothesis that increasing varenicline dosage to 3 milligrams a day is associated with a significant improvement in smoking cessation rates, without a significant increase in side effects,” said Karam-Hage. “Our findings suggest that a subgroup of patients not able to achieve abstinence with the standard dose may benefit from a modest increase in daily varenicline.”

The authors acknowledge several limitations to the study, particularly the non-randomized and open-label design of the study, which may have resulted in selection biases or a placebo effect among those who chose to increase their dosage. To minimize those limitations they employed a sophisticated statistical method known as propensity score analysis, to simulate a controlled and randomized setting.